氨甲喋呤-人血清白蛋白-单抗79结合物在动物体内的组织分布及其稳定性的研究

本研究比较了~(125)标记的氨甲喋呤-人血清白蛋白-单抗79(MTX-HSA-McAb79)和氨甲喋呤-人血清白蛋白(MTX-HSA)两种结合物的血浓度及在肝、脾、肾等重要脏器的组织分布。发现前者的生物利用度大、血的清除率低、且肝脏等重要代谢器官对它的摄取也低。 在MTX-HSA-McAb79结合物的稳定性研究中,首先采用纸层析法及荧光分光光度法分别证明结合物中酰胺键在体内外均具有良好的稳定性;其次采用SDS-PAGE结合放射自显影术,再通过薄层扫描定量,研究了结合物中二硫键的稳定程度。结果表明:二硫键相当不稳定,腹腔注射后1h即有60.5％的二硫键断裂,24h则高达92.9％。r-扫描显示MTX-HSA-McAb79在肿瘤部位的浓集不理想,这与二硫键稳定性试验的结果是一致的。探索新的交联剂和交联方法,增加结合物在体内的稳定性将是今后的目标之一。

Biodistribution and Binding-Stability of MoAb/9-HSA-MTX Conjugates

The blood levels and main tissue concentations of 125I labelled MoAb79-HSA-MTX and HSA-MTX coniugates were compared,The results indicated that MoAb79-HSA-MTX conjugates had not only greater absorption lower blood clearance,but also less taken-up by liver.In the study of the binding-stability of MoAb79-HSA-MTX conjugates,we pro- ved that the amide linkages between MTX and HSA in conjugates had satisfactory stability in vitro and in vivo by TLC and fluorospectrophotometer.The stability of disulfide between HSA and MoAb79 in conjugates was determined by SDS-PAGE electrophoresis plus autoradiography.The results suggested that the disulfide linkages in conjugates were rather instability,60.5% of the bond was split 1 hour after i.p.and up to 92.9%24 hour.The results of instability of disulfide were consistent with those of ***********r-scanning.